Conjugated linoleic acid is an activator and ligand for peroxisome proliferator-activated receptor-gamma (PPARγ)

被引:81
作者
Belury, MA [1 ]
Moya-Camarena, SY
Lu, M
Shi, LL
Leesnitzer, LM
Blanchard, SG
机构
[1] NW Hosp, Dept Mol Med, Bothell, WA 98021 USA
[2] Purdue Univ, Dept Foods & Nutr, W Lafayette, IN 47907 USA
[3] GlaxoSmithKline, Mol Screening, Res Triangle Pk, NC 27709 USA
关键词
conjugated linoleic acid; Delta; 6; desaturase; fatty acid; PPAR gamma; type; 2; diabetes; Wy14,643;
D O I
10.1016/S0271-5317(02)00393-7
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
The goal of the present study was to elucidate the extent that CLA binds to and activates PPARgamma. All of the isomers of CLA tested activated PPARgamma in a manner similar to the polyunsaturated fatty acid, linoleic acid (18:2n6). When the binding affinity of CLA to PPARgamma was determined using a scintillation proximity assay (SPA), isomers of CLA were ligands for PPARgamma with micromolar affinity. To determine the extent that metabolism of CLA via Delta6 desaturase could alter activation of PPARgamma, we used a Delta6 desaturase inhibitor, SC-26,196, to block Delta6 desaturase metabolism. Blocking Delta6 desaturase significantly reduced activation of PPARgamma by c9t11-CLA. These data suggest that the ability of CLA to induce PPAR-responsive genes may be via both direct binding of CLA to the nuclear hormone receptor, PPARgamma, as well as active metabolites of CLA via Delta6 desaturase. Further work is needed to determine the ability of Delta6 desaturase metabolites of CLA to bind and activate PPARgamma. (C) 2002 Elsevier Science Inc. All rights reserved.
引用
收藏
页码:817 / 824
页数:8
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